Tumor antigens of the transplantation type have been identified on the membranes of malignant cells of spontaneous lymphomas occurring in Syrian golden hamsters. This disease is horizontally transmitted to susceptible animals by an unidentified but highly infectious agent with an incidence greater than 50%. This lymphoreticular malignancy in random bred and inbred hamsters constitutes a unique model for the investigation of tumor membrane-associated antigens and their role in the ability of a spontaneous neoplasm to escape immune elimination. The research described in this proposal is directed toward the purification and immunochemical characterization of the lymphoma membrane-associated antigen(s). Solubilization of the antigen(s) will be attempted with nonionic detergents, limited papain digestion, or extraction with 3 M KC1. Subsequent fractionation of membrane extracts will involve gel filtration and ion exchange chromatography in combination with affinity, lectin affinity or hydrophobic chromatography. Specific in vitro and in vivo assays compatible with these methods will be developed for monitoring the antigenicity and transplantation rejection activity during purification. The origin of the lymphoma antigen will be determined as either: 1) an antigen of the causative agent, 2) an agent-directed membrane antigen, 3) a non-agent directed tumor-specific transplantation antigen, or 4) an antigen of fetal origin. True tumor-specific transplantation rejection activity will be determined by the ability of the antigen to interrupt lymphomagenesis. The purified antigen will also be used in preliminary studies defining the humoral and cellular immune responses illicited against the lymphomas. The ultimate objective is a better understanding of the role of tumor-specific membrane antigens in the success of neoplastic disease.